Bifidobacterium longum JBLC-141 alleviates hypobaric hypoxia-induced intestinal barrier damage by attenuating inflammatory responses and oxidative stress

Xiang-Yang Li; Jin Shang; Xiao-Juan Wang; Hui-Ping Ma; Long-Fei Ren; Lei Zhang

doi:10.3389/fmicb.2024.1501999

Bifidobacterium longum JBLC-141 alleviates hypobaric hypoxia-induced intestinal barrier damage by attenuating inflammatory responses and oxidative stress

Front Microbiol. 2024 Dec 17:15:1501999. doi: 10.3389/fmicb.2024.1501999. eCollection 2024.

Authors

Xiang-Yang Li^{1

2

3}, Jin Shang^{1

2

3}, Xiao-Juan Wang^{1

2

3}, Hui-Ping Ma⁴, Long-Fei Ren^{1

2

3

5

6}, Lei Zhang^{1

2

3

5

6}

Affiliations

¹ The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China.
² Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.
³ Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.
⁴ Pharmacy Department, The 940 Hospital of Joint Logistics Support, PLA, Lanzhou, Gansu, China.
⁵ National Clinical key Specialty of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.
⁶ Clinical Research Center for General Surgery of Gansu Province, Lanzhou, Gansu, China.

Abstract

Hypobaric hypoxia exposure occurs at high altitudes, including plateaus, and affects normal intestinal function and microbiota composition. Exposure induces an intestinal inflammatory response and oxidative stress injury, ultimately disrupting intestinal homeostasis and causing barrier damage. Thus, due to its anti-inflammatory, antioxidative, and intestinal microbiota-regulating properties, Bifidobacterium longum is a potentially effective probiotic intervention to protect the intestinal barrier during low-pressure hypoxia on plateaus. However, its mechanism of action is not fully defined. In this study, we investigate the mechanism by which B. longum intervenes in intestinal barrier damage caused by plateau low-pressure hypoxia. To this end, an in vivo model is established by exposing rats to a simulated low-pressure hypoxic plateau environment. The experimental rats were subsequently supplemented with a B. longum strain (JBLC-141) extracted from the feces of healthy adults in Bama, Guangxi. B. longum JBLC-141 mitigates the effects of plateau low-pressure hypoxia on the rat intestinal barrier. This is achieved by activating the intestinal Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway, alleviating plateau hypoxia-induced intestinal oxidative stress injury. B. longum JBLC-141 also attenuates the inflammatory response and upregulates the expression of the tight junction proteins claudin-1, occludin, and zonula occludens-1. Furthermore, it reduces intestinal permeability, effectively ameliorating and repairing the barrier histological damage induced by the plateau low-pressure hypoxic environment. In addition, B. longum JBLC-141 positively regulates the intestinal microbiota, increasing the relative abundance of beneficial bacteria while reducing that of pathogenic bacteria and maintaining intestinal flora homeostasis in rats.

Keywords: Bifidobacterium longum; hypobaric hypoxia; intestinal barrier; intestinal flora; oxidative stress.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Major Science and Technology Special Program Project of Gansu Province (24ZDFA005), the Open Fund of the Key Laboratory of Extreme Environmental Microbiology of Gansu Province (EEMRE202403), the Joint Scientific Research Foundation of Gansu Province (23JRRA1498) and the Scientific Research Project of Outstanding Young talents and talents in Health Industry in Gansu Province (GSWSQN2023-01).